Kent S J, Corey L, Agy M B, Morton W R, McElrath M J, Greenberg P D
Department of Medicine, University of Washington, Seattle 98195.
J Clin Invest. 1995 Jan;95(1):248-56. doi: 10.1172/JCI117647.
Macaca nemestrina has been described as an animal model for acute HIV-1 infection. This animal, unlike most infected humans, appears to contain HIV-1 replication. Therefore analysis of HIV-1-specific proliferative and cytotoxic T lymphocyte (CTL) responses following HIV-1 challenge of M. nemestrina may provide information into the role of such responses in both the control of acute HIV infection and protective immunity. Although CD4+ T cell responses to HIV-1 are generally difficult to detect in HIV-1-infected humans, early and persistent CD4+ T cell proliferative responses to HIV-1 antigens were detected in all HIV-1-inoculated M. nemestrina. HIV-1-specific CD8+ CTL responses were evaluated in PBMC by stimulation with autologous cells expressing HIV-1 genes, limiting dilution precursor frequency analysis, and T cell cloning. CTL reactive with gag, env, and nef were present 4-8 wk after infection, and persisted to 140 wk after infection. The presence of both CD4+ and CD8+ T cell responses before and after clearance of HIV-1 viremia is consistent with a role for these responses in the successful control of HIV-1 viral replication observed in M. nemestrina. Further studies of T cell immunity in these animals that resist disease should provide insights into the immunobiology of HIV-1 infection.
食蟹猴已被描述为急性HIV-1感染的动物模型。与大多数受感染的人类不同,这种动物似乎含有HIV-1复制。因此,对食蟹猴进行HIV-1攻击后,分析HIV-1特异性增殖性和细胞毒性T淋巴细胞(CTL)反应,可能会为这些反应在急性HIV感染控制和保护性免疫中的作用提供信息。虽然在HIV-1感染的人类中通常难以检测到CD4+T细胞对HIV-1的反应,但在所有接种HIV-1的食蟹猴中均检测到了对HIV-1抗原的早期且持续的CD4+T细胞增殖反应。通过用表达HIV-1基因的自体细胞刺激、有限稀释前体频率分析和T细胞克隆,在PBMC中评估了HIV-1特异性CD8+CTL反应。感染后4-8周出现了与gag、env和nef反应的CTL,并持续到感染后140周。在HIV-1病毒血症清除前后,CD4+和CD8+T细胞反应均存在,这与这些反应在食蟹猴中成功控制HIV-1病毒复制中的作用一致。对这些抗病动物的T细胞免疫进行进一步研究,应该能够深入了解HIV-1感染的免疫生物学。